Publication: Blocking Antibodies Targeting the CD39/CD73 Immunosuppressive Pathway Unleash Immune Responses in Combination Cancer Therapies

Published in: Cell Reports, 2019, 27 (8), pp.2411-2425. ⟨10.1016/j.celrep.2019.04.091⟩

Authors: Ivan Perrot, Henri-Alexandre Michaud, Marc Giraudon-Paoli, Severine Augier, Aurelie Docquier, Laurent Gros, Rachel Courtois, Cecile Dejou, Diana Jecko, Ondine Becquart, Helene Rispaud-Blanc, Laurent Gauthier, Benjamin Rossi, Stephanie Chanteux, Nicolas Gourdin, Beatrice Amigues, Alain Roussel, Armand Bensussan, Jean-Francois Eliaou, Jeremy Bastid, Francois Romagne, Yannis Morel, Emilie Narni-Mancinelli, Eric Vivier, Carine Paturel, Nathalie Bonnefoy

Summary

Immune checkpoint inhibitors have revolutionizedcancer treatment. However, many cancers are resis-tant to ICIs, and the targeting of additional inhibitorysignals is crucial for limiting tumor evasion. The pro-duction of adenosine via the sequential activity ofCD39 and CD73 ectoenzymes participates to thegeneration of an immunosuppressive tumor micro-environment. In order to disrupt the adenosinepathway, we generated two antibodies, IPH5201and IPH5301, targeting human membrane-associ-ated and soluble forms of CD39 and CD73, respec-tively, and efficiently blocking the hydrolysis ofimmunogenic ATP into immunosuppressive adeno-sine. These antibodies promoted antitumor immunityby stimulating dendritic cells and macrophages andby restoring the activation of T cells isolated fromcancer patients. In a human CD39 knockin mousepreclinical model, IPH5201 increased the anti-tumoractivity of the ATP-inducing chemotherapeutic drugoxaliplatin. These results support the use of anti-CD39 and anti-CD73 monoclonal antibodies andtheir combination with immune checkpoint inhibitorsand chemotherapies in cancer

Link to Pubmed [PMID] – 31116985

Link to HAL – hal-03241201

Link to DOI – 10.1016/j.celrep.2019.04.091